Document Report Card

ID: ALA1138750

Journal: J Med Chem

Title: Design, synthesis, and biological evaluation of 1,2,3,7-tetrahydro-6h-purin-6-one and 3,7-dihydro-1h-purine-2,6-dione derivatives as corticotropin-releasing factor(1) receptor antagonists.

Authors: Hartz RA, Nanda KK, Ingalls CL, Ahuja VT, Molski TF, Zhang G, Wong H, Peng Y, Kelley M, Lodge NJ, Zaczek R, Gilligan PJ, Trainor GL.

Abstract: A growing body of evidence suggests that CRF(1) receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF(1)) receptor antagonists. Compounds within this series, represented by compound 12d (IC(50) = 5.4 nM), were found to be highly potent CRF(1) receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF(1) antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.

CiteXplore: 15341489

DOI: 10.1021/jm049787k